The usual aim in developing a chemical sensor or biosensor is to produce a signal, which is proportional to the concentration of a specific chemical or set of chemicals (analyte). The sensor usually has two main components, a chemical or biological part that reacts or complexes with the analyte in question (ideally specifically) to form new chemical or biological products or changes in energy that can be detected by means of the second component, a transducer. The chemical/biological component can be said to act as a receptor/indicator for the analyte. A variety of transduction methods can be used including electrochemical (such as potentiometric, amperometric, conductimetric, impedimetric), optical, calorimetric and acoustic. After transduction the signal is usually converted to an electronic digital signal.
Since the signal generated by the chemical/biological reaction with the analyte is usually dependent not only on the concentration of the analyte but also on the characteristics of the sensor itself, such sensors usually require calibration before they can be utilised quantitatively. The way in which the signal varies with the analyte concentration determines the shape of the calibration curve (signal versus analyte concentration) and may define the number of calibration points. Typical calibration curves can be straight line, exponential, s-shaped etc and the principal of calibration applies to all methodologies of transduction for chemical or biological sensors.
Calibration of sensors with an invasive medical application has its own set of specific issues. Invasive or implantable medical sensors are to be presented to the patient in a sterile condition, and are often single use, disposable devices. Ideally, the sensor should be calibrated just before its use since some sensor characteristics that can affect the calibration curve vary with time (ageing effect). It is often the case that the time between sensor manufacture and use can be many months, so calibration at the point of manufacture can lead to inaccuracies in the end result. This means that the attendant clinician or nurse will be required to perform the calibration whilst maintaining sterility of the sensor. Additional constraints applied by the clinician/nurse are that the calibration process should be simple to perform, ideally invisible to the person performing the calibration, and be quickly completed (preferably in less than 10 minutes).
Calibration of many currently available medical sensors requires the clinician/nurse to carry out a number of specific steps which can lead to errors or inaccuracies in the measurement if the process is not followed correctly. There is therefore a need for a more simple calibration process, useful in connection with invasive or implantable sensors, which fulfils the above discussed requirements.
Sterilisation of such devices can also present difficulties. The sterilisation process is typically carried out at the point of manufacture to avoid difficulties with poor or incomplete sterilisation procedures at a hospital or clinic, and to save time on behalf of the clinician or nurse. In the case of glucose, however, glucose-containing solutions have been found to degrade on sterilisation with either heat or gamma-radiation. Thus, the pre-sterilisation of such solutions at manufacture must be avoided. Glucose can instead be provided in solid form, since in this state sterilisation can be carried out without causing degradation. However, the user is then required to make up the required glucose-containing calibration solutions at the point of use. This adds additional steps to the procedure and can be time-consuming. For example over 45 minutes may be required to ensure that glucose has fully dissolved and equilibrated in the solution.
Further, there is a need to maintain sterility during the calibration, a factor which is difficult to achieve given the differing sterilisation processes which may be needed for different parts of the calibration unit and sensor. Sterility will be lost if the process requires the user to break open sterile packages in order to complete calibration.
There is therefore particularly a need for a means of calibrating a glucose sensor which can be carried out under sterile conditions, without loss of sterility during the process, and which can be carried out in a short time.